Method of hydroxylation

ABSTRACT

A process for the production of alcohols and esters comprises hydroxylating a saturated hydrocarbon at between about 20° and about 130° C. with an oxygenated amine. The amine may be a hydroxylated secondary amine or an oxide of a tertiary amine. The reaction medium includes a Lewis acid and a salt of divalent or trivalent iron.

This is a division, of application Ser. No. 622,661, filed: Oct. 15,1975 now U.S. Pat. No. 4,045,498.

BACKGROUND OF THE INVENTION

This invention relates generally to methods for the preparation ofhydroxylated organic compounds and more specifically to the introductionof a hydroxyl group into alkyl and alkylene constituents of organiccompounds.

Although the introduction of hydroxyl groups into saturated aliphaticand alicyclic hydrocarbon compounds by microbiological means has beenknown for many years, satisfactory methods of direct hydroxylation ofthese structures by purely chemical procedures have not been availablein the past. Many oxidative procedures are known which introduceoxygenated functions into saturated hydrocarbon chains; but in general,an undesirable mixture of alcohol, aldehyde, ketone and carboxylic acidresults.

SUMMARY OF THE INVENTION

I have now found that organic compounds containing long alkyl oralkylene chains can be selectively oxidized with the replacement of ahydrogen atom by a hydroxyl group without the formation of higheroxidation products such as carbonyl and carboxyl derivatives. Theomega-minus-one position appears to be the preferential situs forinsertion of the hydroxyl group; and it is believed that a free radicalmechanism is involved.

The present invention is useful in the production of hydroxylated fattyacids, which products have known utility in antibacterial agents and asstarting materials for the preparation of polymers for coatings,plasticizers and lubricants. The present invention is especiallyadvantageous in that the hydroxyl group is inserted in a position remotefrom the active, carboxyl substituent of the fatty acid molecule, ratherthan proximal thereto as might be expected if the reaction were tosucceed at all.

It is therefore an important object of the present invention to providea method of hydroxylating saturated hydrocarbon compounds which employsan intermolecular oxidation technique.

A more general object of the invention is to provide new and improvedmethods of hydroxylating saturated hydrocarbon compounds.

These and other objects and features of the invention will becomeapparent from a consideration of the following descriptions.

DESCRIPTION OF THE PREFERRED EMBODIMENT

According to the present invention, alcohols and esters are preparedfrom the corresponding saturated hydrocarbon by reacting the hydrocarboncompound with an N-oxygenated amine in a medium which includes asuitable Lewis acid, such as trifluoroacetic acid, and a salt of a firstseries transition metal element, such as ferrous carbonate. Uponcompletion of the reaction, the resultant product is separated from theprocessing medium, as by distillation, or by the addition of waterfollowed by extraction with a water-insoluble organic solvent; and inthe event that the reaction product is an ester and the correspondingalcohol is the desired end product, the ester is hydrolyzed to the freealcohol by conventional hydrolytic procedures.

Organic compounds useful as a starting material in the practice of theinvention include alkanes and cycloalkanes having a chain length of atleast four carbon atoms; and one or more of the hydrogen atoms in thecompound may be substituted for by hydroxyl, carboxyl, carboxamide,lower carbalkoxy, halogen, alkoxyl and oxo moieties. In addition, thestarting hydrocarbon compound has the general formula ##STR1## whereinR₁ and R₂ are alkyl groups which have a total of from 3 to 18 carbonatoms and wherein the dotted line represents an optionalcarbon-to-carbon bond. Specific hydrocarbon compounds which have provedparticularly useful in the practice of the present invention include thefollowing:

    ______________________________________                                        heptane         1-tetradecanol                                                decane          2-octanone                                                    cyclodecane     octanoic acid                                                 cyclohexane     1-octanoic amide                                              cycloctane      methyl octanoate                                              cyclododecane   methyl octyl ether                                            1-pentanol      1-chlorooctane                                                1-octanol       1-chloropentane                                               1-decanol       1-aminooctane                                                 1-dodecanol     1-amino-octadecane                                                            stearic acid                                                  ______________________________________                                    

The oxidizing agent for use in inserting a hydroxyl group in thesaturated hydrocarbons described immediately hereinabove isadvantageously an N-oxygenated aliphatic or alicyclic amine or N-mono-and N,N,alkyl derivatives and takes the particular form of trialkylamine oxides and N,N-dialkylhydroxylamines in which the alkyl groupscontain a total of from 2 to 18 carbon atoms. Furthermore, the alkylgroups may be branched or they may be joined to form an oxygenatedcycloalkylamine or they may be joined through an additional nitrogenatom to form mono- or bi-cyclic diamines. Useful alkylhydroxylaminesinclude N,N-diethylhydroxylamine and N-hydroxpiperidine; andrepresentative tertiary amine oxides include trimethylamine oxide,triethylamine oxide and 1,4-diaza-bicyclo(2.2.2)octane N,N-dioxide. Inaddition, a 0.5 to 2.5 molar excess of the oxidizing agent has beenfound to be associated with higher percentage yields of the ultimateester or alcohol.

The medium for reaction of the saturated hydrocarbon compounds and theoxidizing agent comprises a Lewis acid and a catalyst taking the form ofa salt of a first series transition metal element, salts of thedescribed character being known initiators of free-radical reactions.Exemplary Lewis acids in this regard include strong organic acids, suchas trifluoroacetic acid, mineral acids, such as sulfuric acid, andmixtures of organic and mineral acids. Trifluoroacetic acid has provedeminently suitable in the practice of the present invention but iscostly; mixtures of 80% acetic acid and 20% sulfuric acid and 20% or 33%methanesulfonic acid in acetic acid is generally useful; and strongsulfuric acid has relatively poor solvent characteristics except inrelation to molecules that are highly oxygenated.

As stated hereinabove, the catalyst for the reaction of the presentinvention comprises a salt of the first series transition metalelements, that is, salts of iron, cobalt, nickel, vanadium, copper andtitanium; and while salts of these metals in their lower oxidationstates are preferred, higher oxidation states may be employed inasmuchas these latter compounds revert to their lower oxidation states in thefree radical situation. Examplary anions for these salts includecarbonate, sulfate, acetate, hydroxide and ammonium sulfate.

Ferrous carbonate is a particularly advantageous catalyst, especiallywhen the reaction medium is selected to include trifluoroacetic acidbecause the carbonate affords more of the active ferrous ion for a givenaddition in such an environment. Ferrous carbonate may be prepared byadding aqueous 10% sodium carbonate to boiling ferrous ammonium sulfatesolution. A precipitate results and is subjected to multiple washingswith distilled water, the water being separated after each washing bydecantation. Desirably, the precipitated material is protected fromatmospheric air and other sources of oxygen; and after the last washing,the wet ferrous carbonate is placed on a rotary evaporator at 100° C.and 20 torr. The resultant olive-green flakes are stored in a nitrogenatmosphere until use.

The reaction between the saturated hydrocarbon compound and theoxydizing agent proceeds with facility; and temperatures in the range offrom about 20° to about 130° C. produce acceptable results in five days'time or less. Inert atmospheres of nitrogen or carbon dioxide are usefulin increasing yields, although the reaction proceeds reasonably welleven in an atmosphere of air. The reaction product itself may beextracted from the reaction medium with ethyl ether, carbontetrachloride or other suitable solvents and then demoisturized oversolid sodium sulfate and distilled.

When esters are the evident reaction product, they may be readilyhydrolyzed to the corresponding alcohol if desired. Water at ambientroom temperature slowly effects this hydrolysis, and it proceeds rapidlyin the presence of strong bases at 25° C. and in boiling water.

In order to describe the invention more fully, the following specificexamples are given without, however, intending to limit the invention tothe precise details and conditions described except as is set forth inthe appended claims.

EXAMPLE I

A reaction mixture was prepared by adding together 20.0 ml. oftrifluoroacetic acid; 0.65 g. (5 mmol) of 1-octanol; 0.67 g. (6 mmol) oftrimethylamine oxide di-hydrate; and 0.23 g. (2 mmol) of ferrouscarbonate. This mixture was stirred under reflux and a carbon dioxideatmosphere at approximately 75° C. for 5 days. The resulting mixture wasthereafter cooled and diluted to approximately 20% trifluoroacetic acidwith ice water. The diluted mixture was extracted with ethyl ether andthe ethereal liquid washed once with water and then with sufficientaqueous 10% sodium carbonate to give an alkaline solution. The etherextract was then washed a second time with aqueous 10% sodium carbonateand dried over solid sodium sulfate.

Gas chromatograms were obtained on a Barber-Colman Series 5000instrument equipped with a flame ionization detector. The fuel gas was amixture of hydrogen and air, and the carrier gas was nitrogen. The glassU-columns were 0.25 in. × 6 ft.; and 20% SE 30 on 80-100 Gas Chrom W wasused at 150° C. Flow rates were 23 ml.min⁻¹.

The reaction products of the starting material were all present as thecorresponding trifluoroacetates; and gas chromatographic analysis showedthat 70% of the 1-octanol had been converted to octanediols in thefollowing proportions:

    ______________________________________                                        Hydroxy         Relative                                                      Substitution    Proportion                                                    ______________________________________                                        1,7             68%                                                           1,6             23                                                            1,5             8.5                                                           1,4             0.8                                                           ______________________________________                                    

The identification of the foregoing reaction products was supported bynuclear magnetic resonance spectroscopy.

EXAMPLES II and III

The general procedure of Example I was repeated substituting cyclohexaneas the starting hydrocarbon material, using 100% stoichiometric excessof each of triethylamine oxide and diethylhydroxylamine in separateruns, and employing ferrous sulphate as the catalyst. Yields were on theorder of 50% conversion of the starting material.

EXAMPLES IV AND V

The procedure of Example I was employed using decane as the startinghydrocarbon material, 40 mol-percent ferrous carbonate as catalyst, anda 10% excess of trimethylamine oxide. A conversion of 86% was obtainedof which 81% was monohydroxylated and 5% was dihydroxylated.

Decane was also successfully hydroxylated in a medium comprising 20%sulfuric acid in acetic acid.

EXAMPLE VI

The procedure of Example I was again followed generally but utilizingcyclododecanol and trimethylamine oxide as the reactants, the latter in100% excess. A 50% conversion was achieved.

EXAMPLES VII, VIII and IX

Using the general procedure of Example I and employing 20% excesstrimethylamine oxide as the oxidizing agent, 1-dodecanol and1-tetradecanol were converted to the corresponding dihydroxy compoundsand 2-octanone was converted to 7-hydroxy-2-octanone.

EXAMPLE X

Using the general procedure of Example I and 100% excess oftrimethylamine oxide as the oxidizing agent, octanoic acid was convertedto a mixture of the trifluoroacetates of hydroxyoctanoic acid in a 66%yield.

EXAMPLES XI, XII, XIII and XIV

Octanoamide, 1-chlorooctane, stearic acid and methyl octyl ether werealso successfully hydroxylated using trimethylamine oxide as thereactant.

The specific examples herein described are to be considered as beingprimarily illustrative only. Various changes beyond those describedwill, no doubt, occur to those skilled in the art; and such changes areto be understood as forming a part of this invention insofar as theyfall within the spirit and scope of the appended claims.

The invention is claimed as follows:
 1. The process of preparingalcohols by single-carbon hydroxylation, which comprises the steps of:reacting a saturated hydrocarbon compound with an N-oxygenated amine ina medium including a Lewis acid and a salt of a first series transitionmetal element; and separating the reaction product from said medium, inwhich the saturated hydrocarbon compound has the general formula##STR2## wherein R₁ and R₂ are hydrocarbon groups which have combined atotal of from 4 to 18 carbon atoms and wherein the dotted linerepresents an optional carbon-to-carbon bond, R₁ and R₂ being alkylgroups when said bond is absent and R₁ and R₂ being alkylene groups whensaid bond is present. and wherein one of R₁ and R₂ includes a carboxylmoiety.
 2. The process according to claim 1 in which the saturatedhydrocarbon is methyl octanoate.
 3. The process according to claim 1 inwhich the saturated hydrocarbon is stearic acid.